tbuckley/cabot-search huggingface dataset:
False positive PET scan in patients with treated malignancy following COVID-19 vaccination.
Authors: Alexander Antoni Slota, Vrajesh Parmar, Amy M. Weise, Ding Wang
Journal: Journal of Clinical Oncology (2023)

e18698 Background: The COVID-19 pandemic led to mass vaccination across the globe and resulted in several unintended consequences, one of which being reactive lymphadenopathy mimicking malignancy. A large study reported hypermetabolic lymphadenopathy (HLN) in over 45% of patients after receiving at least one dose of COVID-19 vaccine. A study on breast cancer patients noted a near-400% increase in lymphadenopathy on MRI and ultrasonography over the two years prior to mass vaccination. These findings present a dilemma in patients with treated malignancy while under surveillance. As vaccination became more commonplace, a case series reported on patients with PET-detected lymphadenopathy, with biopsies confirming VRLN. These investigations contributed to general recommendations on the importance of clinical context in patient care after COVID-19 vaccination. We present a unique study that evaluates patients with treated solid and hematological malignancies that presented with HLN after COVID-19 vaccination which emphasizes the importance of clinical acumen in the management of oncological patients in the pandemic era. Methods: We identified 6 patients aged 39-95 with prior malignancy. 5 were diagnosed with metastatic melanoma, and one had a diagnosis of high-grade B-cell lymphoma. Patients were managed with chemotherapy, immunotherapy, surgery, radiotherapy, or a combination of modalities, and were in complete radiological remission. All patients received at least two doses of a COVID-19 vaccine, with one dose at least three weeks prior to a routine surveillance PET-CT. Each patient exhibited HLN. Results: Of six patients, three underwent biopsy. There was no evidence of malignancy in any biopsy, and VRLN was confirmed. The remaining patients were followed with surveillance, and all had resolution of HLN without intervention. Time between COVID-19 vaccination and PET evidence of HLN ranged from 19 to 232 days. Time between first positive and first resolved PET ranged from 92 to 463 days. All patients were alive at the time of abstract submission. Conclusions: Our study emphasizes the importance of a focused history when suspecting recurrent malignancy, especially after sustained remission in our vulnerable populations. Acknowledging that COVID-19 vaccination can lead to HLN is becoming more common, and we show that this can occur, persist, and resolve even months after vaccination. While high suspicion for recurrence should be maintained, all efforts should be taken to protect patients and prevent unnecessary procedures. Records of recent vaccinations should be available and reviewed prior to radiological studies and clinical decisions, which can reduce avoidable interventions and harm. Surveillance of our patients proved to be an appropriate approach, and our study shows that similar patient presentations can have different paths of care depending on the awareness of treating physicians.
Nutritional program among patients with prostate cancer receiving androgen deprivation therapy (ADT).
Authors: Dr. Paulo Sergio Lages, Daniel Vargas Pivato de Almeida, Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Michelle Barbosa, Camila Rosa Dutra
Journal: Journal of Clinical Oncology (2023)

12072 Background: Treatment with ADT can lead to changes in body composition, including an increase in body fat and a decrease in muscle mass. To minimize the nutritional risks associated with ADT, a nutritional program was developed. Thus, this study sought to determine the benefit of this program among patients with prostate cancer receiving ADT. Methods: Patients were recruited in a cancer center located in Brasilia, Brazil. Patients were eligible if they were diagnosed with prostate cancer, and about to initiate treatment with ADT. They were assessed before starting ADT and at follow-up assessment (3 months). Based on their risk, patients were instructed to follow either a normocaloric (20-25 kcal/kg) or a hypocaloric (18-20 kcal/kg) diet, and both groups were required to consume a hyperproteic diet (1-1.2 g/kg), including the use of whey protein supplementation as needed. Outcomes measures included nutritional risk (Patient-Generated Subjective Global Assessment; PG-SGA), body composition (Medical software Lookin’Body120), and muscle strength (Jamar Hydraulic Hand Dynamometer). Descriptive statistics were generated, and paired T-test, Wilcoxon signed rank on paired samples and ANOVA-RM were used to evaluate changes in variables over time. Results: A total of 62 patients were included in this program. Participants had a median age of 75 years (range from 41-97) and were predominantly married (87%). A great proportion of patients (65%) were diagnosed with a stage IV disease. Notably, 23% were diagnosed with moderate to severe nutritional risk at baseline; 47% were overweight, 13% were obese and 14% were with sarcopenia. The nutritional program resulted in maintenance of total body weight (median 74.1 vs 75.6 kg, P=0.12), lean body weight (median 29.1 vs 29.4 kg, P=0.11), and muscle strength (median 30 vs 30 kg, P=0.62), while a statistically significant loss of body fat weight (median 22.0 vs 20 kg, P=0.003) was found over the 12-week period. Despite no change in the PG-SGA scores were noted overtime, the rate of sarcopenia has decreased (15% vs 13%, P=0.03) and the proportion of eutrophic patients has increased (18% vs 27%, P=0.001), as seen in the contingency table below. Conclusions: These findings suggest that this program may improve body composition and maintain muscle strength in men receiving treatment with ADT after only three months of intervention. Future studies should validate the benefit of this program in randomized trial with a longer follow-up assessment (6 and 12 months after treatment initiation). [Table: see text]
Spatial distribution of B cells and lymphocyte clusters for the treatment of non-small cell lung cancer.
Authors: Corinne Ramos, Amandine Gerstenberg, Melodie Boute, Adele Ponzoni, Jonathan Stauber
Journal: Journal of Clinical Oncology (2023)

2622 Background: The presence of tertiary lymphoid structure (TLS) in tumor tissues has been reported to be a factor associated with a good prognosis in several types of cancers including non-small cell lung cancer (NSCLC). However, the relationship between TLS spatial organization and the treatment response remains unknown in NSCLC who received ant-PD-1 antibody. The purpose of this study was to evaluate the effect of the various stages of the spatial organization of the TLS from locally concentrated aggregates of immune cells, through clearly defined B cell follicles to mature follicles in NSCLC and its relationship with the tumor microenvironment on anti-PD1 treatment response. Methods: Frozen sections from retrospectively collected surgically resected NSCLC tumors treated with adjuvant pembrolizumab therapy were used. The TLS in tumor tissues was detected by high-plex imaging mass cytometry staining and the difference in TLS spatial organization was compared to the features of the tumor microenvironment and the objective response rate of the patients. Results: TLS identified and characterized according to their spatial organization within or adjacent to the tumor showed that the presence of tumor-associated TLS (TA-TLS) correlated with favorable response to anti-PD-1 therapy. The abundance and the spatial distribution of B cells allowed for a better definition of the correlation between B cell subsets with clinical outcomes showing that the heterogeneity in these TA-TLS influences the predictivity significance to anti-PD-1 therapy. Conclusions: Identifying the phenotypic heterogeneity of intratumor B cells and their functional connection to CD8 T cell helps optimally guide the anti-PD-1 treatment strategy. This spatial mechanistic insight also provides an exciting opportunity for translation of B cell-based immunotherapies into clinics complementary to existing T cells centric strategies.
Phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma with variant histologies (RCCvh).
Authors: Bradley Alexander McGregor, Jiaming Huang, Wanling Xie, Wenxin Xu, Mehmet Asim Bilen, David A. Braun, Tian Zhang, Rana R. McKay, David F. McDermott, Hans J. Hammers, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2023)

4520 Background: New therapeutic approaches in RCCvh are needed. Herein, we report on treatment intensification with the combination of Cabo/Nivo/Ipi in patients with metastatic RCCvh in a multi-institutional prospective single arm phase II trial. (NCT04413123). Methods: Eligible patients (pts) had metastatic RCCvh with ECOG performance status of 0-1 and may have received one line of prior therapy excluding immunotherapy or Cabo. Pts underwent a baseline biopsy and received treatment with Nivo 3 mg/kg and Ipi 1 mg/kg intravenously Q3 weeks (W) for 4 cycles followed by Nivo 480 mg IV Q4W. Cabo was given continuously at dose of 40 mg daily; reductions to 20 mg daily and 20 mg every other day were allowed. The primary endpoint was objective response rate (ORR) by RECIST 1.1. Safety was a secondary endpoint. Results: 40 pts have been enrolled. At the time of data cut-off (Dec 9, 2022), 38 pts received at least 1 study drug. 11% (n=4) pts received prior systemic therapy. 45% (n=17) received all 4 doses of Nivo and Ipi; 18% (n=7) received 3 and 37% (n=14) received ≤ 2 doses. 61% (n=23) (15 of whom received 4 cycles Nivo/Ipi) received Nivo maintenance (median number of cycles, 5 (range, 1-21)). 71% (n=27) and 13% (n=5) required Cabo dose reduction to 20 mg and 20 mg every other day, respectively. Median follow-up was 8.4 (range, 2.1-23) months. Objective response was achieved in 8 pts (ORR 21%, two-sided 80% CI, 13%-32%). Median duration of response was not reached with 5 pts maintaining response &gt; 6 months. Median progression-free survival was 8.9 (95% CI, 4.2-12.7) months. 74% (n=28) developed treatment-related grade 3 or higher toxicities; 37% (n=14) developed ≥ grade 3 elevation in AST or ALT. 29% (n=11) required high dose steroids (prednisone ≥ 40 mg daily or equivalent). 13% (n=5) discontinued all study drugs due to toxicity. No grade 5 toxicity has been reported. Conclusions: The study suggests activity for this combination in patients with RCCvh particularly among those without chromophobe histology. An additional cohort of 20 pts is enrolling with Cabo starting dose of 20 mg daily. Clinical trial information: NCT04413123 . [Table: see text]
Real-time customized precision combination therapies based on potential actionability and coalterations to provide therapeutic opportunities for hyperprogressive disease after immune checkpoint inhibitor therapy.
Authors: Lili Wang, Haitao Wang, Hong Zheng Li
Journal: Journal of Clinical Oncology (2023)

e14688 Background: Patients with hyperprogressive disease (HPD) after immune checkpoint inhibitor therapies have few treatment options and short survival times. Genomic-based precision medicine within the frame of molecular tumor board might theoretically enable effective treatment identification for HPD. Detailed data on MTB guided treatments and outcome with a focus on HPD have not been reported yet. Methods: This is a single-institution retrospective, open-label, histology-agnostic analysis of the consecutively identified HPD patients that have received a real-time precision combination treatment approach which would rapidly integrate clinical grade targeted next-generation sequencing, NGS interpretation and with or without patient-derived xenografting to identify and prioritize effective customized targeted combination treatments within the frame of molecular tumor board at the Tianjin Medical University Second Hospital, a single large academic medical center, refractory cancer-foucused, between January 2018 and January 2022. Treatment was selected using on-label, off-label or investigational agents either in monotherapy or in combination. Clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, outcomes, response assessment based on radiologic imaging and follow-up data were assessed through database searching. Results: A total of 41 HPD suspected patients were referred to the MTB, and 38 conformed HPD with one of the criteria of Russo or Kato. 27 patients were treated with MTB recommended targeted mono or combinational therapy, 4 in accordance with guidelines (on label) in clinical practice, and 23 off label within two ongoing real-time precision medicine programme for patients with exhausted standard care. Of 25 evaluable patients, 20 (80%) achieved either partial response (n = 13, 52%) or stable disease (n = 7, 28%) and with a median overall survival of 12.2 months (95% CI, 8.4 months to not reached). Furthermore, 14 (56%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. Conclusions: It represents a proof of-concept case series as it demonstrates the feasibility of real time precision approach in the clinical setting and guide individual patient treatment in the rare and high aggressive disease. Patients with MTB-recommended treatments seemed to benefit with respect to PFS ratio and OS.
Update for NCI-COG Pediatric MATCH: Active trial cohorts for children, adolescents and young adults with refractory cancers.
Authors: Donald Williams Parsons, Katherine A. Janeway, Theodore Willis Laetsch, Meredith Irwin, Elizabeth Alva, Christine A. Pratilas, Andrea Flynn Franson, David R. Patton, Lauren Saguilig, Jin Piao, Todd Allen Alonzo, Stacey L. Berg, Elizabeth Fox, Douglas S. Hawkins, Margaret M. Mooney, Naoko Takebe, James V. Tricoli, Nita Seibel
Journal: Journal of Clinical Oncology (2023)

TPS10071 Background: The National Cancer Institute–Children's Oncology Group Pediatric Molecular Analysis for Therapy choice (MATCH) trial seeks to facilitate evaluation of molecular-targeted therapies in biomarker-selected cohorts of childhood and young adult patients with cancer by screening tumors for actionable alterations. The Pediatric MATCH screening protocol and first seven treatment arms were activated in July 2017 for patients treated at COG sites across the United States; six additional treatment arms were activated between 2017 and 2020. In 2022 a major screening protocol amendment discontinued centralized tumor testing at MATCH laboratories and mandated use of molecular profiling reports from outside laboratories to determine treatment arm eligibility. Methods: The trial assigns patients aged 1 to 21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms of molecularly-targeted therapies based on the genetic alterations detected in their tumor. Starting in January 2022, a clinical tumor molecular profiling report from a CAP/CLIA-approved laboratory has been required for patients to enroll in the screening protocol. The treating site indicates which molecular alteration in the submitted report is believed to be actionable as well as the open Pediatric MATCH study arm for which the patient is proposed to be eligible. The submitted report is then reviewed by the study Molecular Review Committee to determine if an actionable alteration is present (based upon study-defined levels of preclinical and clinical evidence): if so, the patient is assigned to the relevant MATCH treatment arm. Other treatment arm eligibility requirements are typical of phase 2 pediatric trials including adequate patient performance status and standard washout periods for prior therapy. Each treatment arm follows a one (arms A, D, F, M, N) or two (arm K) stage design with a 20 patient primary cohort and option for histology-specific expansion cohort(s) if at least 3 objective responses are seen in a tumor histology. The primary endpoint is objective response rate; secondary endpoints include safety/tolerability and progression-free survival. Therapy is discontinued if there is evidence of progressive disease or drug related dose-limiting toxicity that requires removal from therapy; therapy may otherwise continue for up to 2 years. As of January 2023, 6 of the 13 Pediatric MATCH treatment arms remain open to enrollment (Table). Clinical trial information: NCT03155620 . [Table: see text]
Examination of real-world data from geriatric assessments in a comprehensive cancer center to explore predominant and cancer-specific domains for intervention.
Authors: Kaitlyn Pelletier, Ishwarya Balasubramanian, Kamal Kant Sahu, Jessica Cohan, Manish Kohli, Benjamin L. Maughan, Umang Swami, Neeraj Agarwal, Sumati Gupta
Journal: Journal of Clinical Oncology (2023)

e24027 Background: Older adults (OA) with cancer have a higher risk of harm with cancer treatment. Geriatric Assessment (GA) based treatment modifications can help mitigate toxicity and functional impairment. The Geriatric Oncology Assessment and Plan (GOAL) Clinic was established with the aim of providing age-friendly care to OA with cancer at Huntsman Cancer Institute. This retrospective study presents the needs identified using GA in the real-world setting. Methods: Patients (pts) aged ≥65 years are referred to the GOAL clinic by their oncologists/hematologists for age-related concerns. A geriatrics nurse practitioner administers a GA upon initial visit, communicates specific age-related concerns with the referring provider, and subsequently manages any geriatric syndromes that may interfere with their treatment tolerance or outcomes. We analyzed GA data to identify the specific needs of OA with cancer referred to the GOAL clinic. Results: We evaluated 222 pts in the GOAL clinic between September 2020 and January 2023. The median age was 77 years, 52% were female. The most common cancer diagnosis was prostate, followed by breast, colorectal, pancreatic, and bladder. Of the pts assessed, the median Eastern Cooperative Oncology Group (ECOG) was 1, and the median body mass index (BMI) was 26.4 kg/m 2 . 12% of pts had a moderate to high risk for malnutrition. A Patient Health Questionnaire-9 (PHQ-9) showed minimal, mild, moderate, moderately severe, and severe depression in 35%, 20%, 14%, 7%, and 3% of pts, respectively. The Generalized Anxiety Disorder scale-7 (GAD-7) showed minimal, mild, moderate, and severe anxiety symptoms in 35%, 19%, 9%, and 7% of pts respectively. The median Mini-cog score was 4, and those who reflexed to testing with Montreal Cognitive Assessment (MOCA) had a median score of 22 out of 30 suggesting mild cognitive impairment (MCI). A greater proportion of pts with prostate cancer (PC) were overweight and had MCI by MOCA (Table 1). Multidisciplinary interventions were implemented, and GA was used to determine the appropriateness of cancer treatment. Conclusions: Cognitive dysfunction and depression were this population's most common geriatric syndromes. PC pts had a higher median BMI and greater proportion of patients with MCI than pts with other cancers. Dysmetabolic syndrome associated with elevated BMI is not a domain of GA but is pertinent to treatment toxicity in PC. MCI is not apparent on a routine oncology evaluation. Interventions are needed to prevent, screen, and treat MCI in OA with cancer, especially PC, and dysmetabolic syndrome in OA with PC.[Table: see text]
Dynamic ctDNA to inform the precise management of resected NSCLC: LUNGCA-2 study.
Authors: Liang Xia, Qiang Pu, Ran Kang, Jiandong Mei, Lu Li, Ying Yang, Senyi Deng, Gang Feng, Lin Ma, Feng Lin, Hu Liao, Chengwu Liu, Yunke Zhu, Qingyun Li, Xiaolong Zhang, Lunxu Liu
Journal: Journal of Clinical Oncology (2023)

8528 Background: Circulating tumor DNA (ctDNA) has been reported to be valuable for minimal residual disease (MRD) detection, but there is a lack of studies comprehensively assessing whether dynamic ctDNA monitoring can inform whole-course precise postoperative cancer management. In the present study (LUNGCA-2), we analyzed data obtained from longitudinal ctDNA monitoring of stage I-III NSCLC patients in the LUNGCA cohort, and sought to assess the use of dynamic ctDNA monitoring for precise whole-course postoperative management of NSCLC patients. Methods: All eligible NSCLC patients underwent curative-intent surgery and subsequently received adjuvant therapies when indicated by clinical practice guidelines for NSCLC. The clinical follow-up was scheduled to be every 3-6 months mainly involving CT and/or MRI. Fresh frozen or paraffin-embedded tissues of primary tumors were collected intraoperatively for baseline somatic mutation profiling. Blood samples were collected before surgery, at 3 days and 1 month after surgery, and then every 3-6 months at clinical visits up to 3 years postoperatively. 233 patients with a total of 2123 plasma samples were ultimately included in the longitudinal ctDNA analysis in the current study. NGS assays were performed with a custom-designed panel that covered 769 cancer-related genes via the MinerVA platform (Genecast Biotechnology Co., Ltd). Results: Among the cohort, 166 patients harboring targetable mutations in the primary tumor tissue, 15 were preadjuvant ctDNA positive, and among them, only 25% patients treated with adjuvant TKI therapy experienced relapse during follow-up, and patients received ACT or no adjuvant therapy had a relapse rate of 100%. TKI treatment tended to improve RFS compared with no treatment (HR 0.1, P = 0.025), but ACT failed to improve RFS (HR 1.1, P = 0.834). Among all 82 patients receiving adjuvant therapy, the pre- and post-adjuvant therapy postoperative ctDNA status with a negative-negative or positive-negative pattern had similar and favorable RFS ( P = 0.545) but that patients with a positive-positive or negative-positive pattern had significantly inferior RFS than those with a negative-negative pattern (both P &lt; 0.001). For recurrence monitoring, posttreatment ctDNA MRD status had a positive predictive value of 100% and a negative predictive value of 91.8%, and the sensitivity of MRD detection was affected by the organ of relapse. Among positive ctDNA MRD patients, faster increase of ctDNA concentration correlated with more imminent clinical relapse. The median lead time from ctDNA detection to radiological relapse was 273 days. Moreover, ctDNA negativity after relapse was associated with favorable survival. Conclusions: These findings highlight the clinical significance of ctDNA dynamics for the precise whole-course postsurgical management of NSCLC patients.